ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1627G>A (p.Val543Met) (rs794727134)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724023 SCV000226184 uncertain significance not provided 2018-06-25 criteria provided, single submitter clinical testing
GeneDx RCV000724023 SCV000241509 uncertain significance not provided 2018-03-12 criteria provided, single submitter clinical testing The V543M variant has been previously reported in an individual with benign familial neonatal seizures; the variant was also identified in the affected father and 2 paternal aunts (Lee et al., 2017). Functional studies demonstrate the V543M variant causes a mild electrophysiological change in channel function compared to wild type (Lee et al., 2017). Missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with with KCNQ2-related disorders (Stenson et al., 2014). The V543M variant is observed in 1/108796 (0.001%) alleles from individuals of European background (Lek et al., 2016). However, the V543M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics RCV000720278 SCV000851155 likely pathogenic Seizures 2017-03-01 criteria provided, single submitter clinical testing Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Fulgent Genetics,Fulgent Genetics RCV000765493 SCV000896789 uncertain significance Benign familial neonatal seizures 1; Early infantile epileptic encephalopathy 7 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001240137 SCV001413061 uncertain significance Early infantile epileptic encephalopathy 2019-11-13 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 543 of the KCNQ2 protein (p.Val543Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with early onset seizures (PMID: 28399683, 31199083, 29056246). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 194446). This variant has been reported to affect KCNQ2 protein function (PMID: 28399683). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000781975 SCV000920430 likely pathogenic Benign familial neonatal seizures 1 2016-11-15 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.